| 1. |
- Ali, Neserin, et al.
(författare)
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Analysis of nanoparticle-protein coronas formed in vitro between nanosized welding particles and nasal lavage proteins.
- 2016
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Ingår i: Nanotoxicology. - : Taylor & Francis. - 1743-5390 .- 1743-5404. ; 10:2, s. 226-234
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Tidskriftsartikel (refereegranskat)abstract
- Welding fumes include agglomerated particles built up of primary nanoparticles. Particles inhaled through the nose will to some extent be deposited in the protein-rich nasal mucosa, and a protein corona will be formed around the particles. The aim was to identify the protein corona formed between nasal lavage proteins and four types of particles with different parameters. Two of the particles were formed and collected during welding and two were manufactured iron oxides. When nasal lavage proteins were added to the particles, differences were observed in the sizes of the aggregates that were formed. Measurements showed that the amount of protein bound to particles correlated with the relative size increase of the aggregates, suggesting that the surface area was associated with the binding capacity. However, differences in aggregate sizes were detected when nasal proteins were added to UFWF and Fe2O3 particles (having similar agglomerated size) suggesting that yet parameters other than size determine the binding. Relative quantitative mass spectrometric and gel-based analyses showed differences in the protein content of the coronas. High-affinity proteins were further assessed for network interactions. Additional experiments showed that the inhibitory function of secretory leukocyte peptidase inhibitor, a highly abundant nasal protein, was influenced by particle binding suggesting that an understanding of protein function following particle binding is necessary to properly evaluate pathophysiological events. Our results underscore the importance of including particles collected from real working environments when studying the toxic effects of particles because these effects might be mediated by the protein corona.
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| 2. |
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| 3. |
- Benjamins, Jan-Willem, et al.
(författare)
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New experimental setup to use ellipsometry to study liquid-liquid and liquid-solid interfaces
- 2002
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 18:16, s. 6437-6444
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Tidskriftsartikel (refereegranskat)abstract
- Different types of optical light guides were constructed and tested to enable convenient multiple angle of incidence ellipsometry, on solid and liquid interfaces in liquid solutions. Two light guides are needed on an ellipsometer, one to guide the incoming light and one to guide the light that is reflected at the test surface, and therefore one light guide was mounted on the laser arm and one on the detector arm of the ellipsometer. With this arrangement the optical windows automatically adjust to always be perpendicular to the direction of the light independent of the angle of incidence. The purpose with these light guides is to facilitate the passage of light through the air/solution interface. A thorough theoretical and experimental analysis of optical errors introduced by such light guides is presented. This discussion includes the effect of multiple reflections between and within the windows of the light guides' On the basis of this analysis a new ellipsometry setup with light guides, consisting of glass tube's with glued end windows, was developed. This setup makes it possible to perform accurate measurements in almost any type of measuring cell at any angle of incidence.
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| 4. |
- Björkman, Tommy, et al.
(författare)
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Attitudes towards people with mental illness: a cross-sectional study among nursing staff in psychiatric and somatic care.
- 2008
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Ingår i: Scandinavian Journal of Caring Sciences. - : Wiley. - 1471-6712 .- 0283-9318. ; 22:2, s. 170-177
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Tidskriftsartikel (refereegranskat)abstract
- Stigma and discrimination have been identified as important obstacles to the integration of people with mental illness in society. In efforts to reduce stigma and discrimination, health professionals play an important role as they have frequent contact with and responsibility for treatment and rehabilitation of consumers. The aim of the present study was to investigate attitudes towards mental illness and people with mental illness among nursing staff working in psychiatric or somatic care. The sample consisted of 120 registered or assistant nurses who were interviewed about intimacy with mental illness and attitudes about seven different mental illnesses. The results showed that nursing staff in somatic care, to a higher degree than nursing staff in mental health, reported more negative attitudes with regard to people with schizophrenia as being more dangerous and unpredictable. In contrast, professional experience, intimacy with mental illness and type of care organization were found to be more associated with attitudes to specific mental illnesses concerning the prospect of improvement with treatment and the prospect of recovery. In conclusion, attitudes among nursing staff are in several respects comparable with public opinions about mental illness and mentally ill persons. In order to elucidate if negative attitudes about dangerousness and unpredictability of persons with specific mental illnesses are associated with realistic experiences or with prejudices further studies with a qualitative design are suggested.
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| 5. |
- Cárdenas, Marité, et al.
(författare)
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The interaction between DNA and cationic lipid films at the air-water interface
- 2005
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Ingår i: Journal of Colloid and Interface Science. - : Elsevier BV. - 1095-7103 .- 0021-9797. ; 286:1, s. 166-175
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Tidskriftsartikel (refereegranskat)abstract
- The interaction between DNA and positively charged dioctadecyldimethylammonium bromide (DODAB) and DODAB/disteroylphosphatidylcholine (DSPC) monolayers at the air-aqueous interface was studied by a combination of the surface film balance and Brewster angle microscopy. In presence of DNA, the &UPi;-A isotherm of the cationic monolayer shifts to larger mean molecular areas due to the electrostatic interaction with DNA while the typical liquid expanded-liquid condensed phase transition for DODAB monolayers disappear and the monolayer remains to be in the liquid expanded phase. Furthermore, the morphology of the film dramatically changes, where the large dendritic-like condensed aggregates observed for DODAB monolayers vanish. The charge density of the monolayer was varied by using mixed monolayers with the zwitterionic DSPC and no large effect was observed on the interaction with DNA. By modeling the electrostatic interactions with the linearized Poisson-Boltzmann equation using the finite-element method and taking into account the assumption in the dielectric constants of the system, it was possible to corroborate the expansion of the cationic monolayer upon interaction with DNA as well as the fact that DNA does not seem to penetrate into the monolayer. © 2005 Elsevier Inc. All rights reserved.
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| 6. |
- Carrera-Bastos, Pedro, et al.
(författare)
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C-reactive protein in traditional melanesians on Kitava
- 2020
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Ingår i: BMC Cardiovascular Disorders. - : Springer Science and Business Media LLC. - 1471-2261. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: Population-based levels of the chronic low-grade systemic inflammation biomarker, C-reactive protein (CRP), vary widely among traditional populations, despite their apparent absence of chronic conditions associated with chronic low-grade systemic inflammation, such as type 2 diabetes, metabolic syndrome and cardiovascular disease. We have previously reported an apparent absence of aforementioned conditions amongst the traditional Melanesian horticulturalists of Kitava, Trobriand Islands, Papua New Guinea. Our objective in this study was to clarify associations between chronic low-grade systemic inflammation and chronic cardiometabolic conditions by measuring CRP in a Kitava population sample. For comparison purposes, CRP was also measured in Swedish controls matched for age and gender. Methods: Fasting levels of serum CRP were measured cross-sectionally in ≥ 40-year-old Kitavans (N = 79) and Swedish controls (N = 83). Results: CRP was lower for Kitavans compared to Swedish controls (Mdn 0.5 mg/L range 0.1—48 mg/L and Mdn 1.1 mg/L range 0.1—33 mg/L, respectively, r =.18 p =.02). Among Kitavans, there were small negative associations between lnCRP for CRP values < 10 and total, low-density lipoprotein (LDL) and non-high-density lipoprotein (non-HDL) cholesterol. Among Swedish controls, associations of lnCRP for CRP values < 10 were medium positive with weight, body mass index, waist circumference, hip circumference and waist-hip ratio and low positive with triglyceride, total cholesterol-HDL cholesterol ratio, triglyceride-HDL cholesterol ratio and serum insulin. Conclusions: Chronic low-grade systemic inflammation, measured as CRP, was lower among Kitavans compared to Swedish controls, indicating a lower and average cardiovascular risk, respectively, for these populations.
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| 7. |
- Chouliara, Manto, et al.
(författare)
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Single-cell measurements of two-dimensional binding affinity across cell contacts
- 2021
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Ingår i: Biophysical Journal. - : Elsevier BV. - 0006-3495. ; 120:22, s. 5032-5040
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Tidskriftsartikel (refereegranskat)abstract
- The two-dimensional (2D) affinity between protein molecules across contacting cells is a key parameter regulating and initiating several cellular processes. However, measuring 2D affinity can be challenging, and experimental data are limited. In addition, the obtained 2D affinities are typically averaged over the cell population. We here present a method to measure 2D affinity on single cells binding to polyhistidine-tagged fluorescent ligands anchored to a supported lipid bilayer (SLB). By decreasing the density of ligands in the SLB using imidazole, a new steady-state accumulation in the contact is obtained, and from this change, both the 2D affinity and the number of receptors on the cell can be determined. The method was validated on an SLB containing rat CD2 binding to the rat CD48 mutant T92A expressed on Jurkat T cells. The addition of imidazole did not influence the average 2D affinity (1/Kd), and the spread in affinities within the cell population was low, Kd = 4.9 ± 0.9 molecules/μm2 (mean ± SD), despite an order of magnitude spread in ligand accumulation because of differences in receptor density. It was also found that cell contact size increased both with ligand density and with the number of receptors per cell but that the contact size stayed approximately constant when lowering the ligand density, above a density of around 10 rat CD2 molecules/μm2, after the contact first had formed, indicative of a heterogeneous process. In summary, this method not only allows for single-cell affinities to be measured, but it can also reduce measurement and analysis time and improve measurement accuracy. Because of the low spread in 2D Kd within the cell population, the analysis can further be restricted to the cells showing the strongest binding, paving the way for using this method to study weak binding events.
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| 8. |
- Comasco, Erika, 1982-, et al.
(författare)
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Genetic and Functional Study of L-Type Amino Acid Transporter 1 in Schizophrenia
- 2017
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Ingår i: Neuropsychobiology. - Basel : S. Karger. - 0302-282X .- 1423-0224. ; 74:2, s. 96-103
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Tidskriftsartikel (refereegranskat)abstract
- Schizophrenia involves neural catecholaminergic dysregulation. Tyrosine is the precursor of catecholamines, and its major transporter, according to studies on fibroblasts, in the brain is the L-type amino acid transporter 1 (LAT1). The present study assessed haplotype tag single-nucleotide polymorphisms (SNPs) of the SLC7A5/LAT1 gene in 315 patients with psychosis within the schizophrenia spectrum and 233 healthy controls to investigate genetic vulnerability to the disorder as well as genetic relationships to homovanillic acid (HVA) and 3-methoxy-4-hydroxyphenylglycol (MHPG), the major catecholamine metabolites in the cerebrospinal fluid (CSF). Moreover, the involvement of the different isoforms of the system L in tyrosine uptake and LAT1 tyrosine kinetics were studied in fibroblast cell lines of 10 patients with schizophrenia and 10 healthy controls. The results provide suggestive evidence of individual vulnerability to schizophrenia related to the LAT1 SNP rs9936204 genotype. A number of SNPs were nominally associated with CSF HVA and MHPG concentrations but did not survive correction for multiple testing. The LAT1 isoform was confirmed as the major tyrosine transporter in patients with schizophrenia. However, the kinetic parameters (maximal transport capacity, affinity of the binding sites, and diffusion constant of tyrosine transport through the LAT1 isoform) did not differ between patients with schizophrenia and controls. The present genetic findings call for independent replication in larger samples, while the functional study seems to exclude a role of LAT1 in the aberrant transport of tyrosine in fibroblasts of patients with schizophrenia.
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| 9. |
- Dam, Tommy, et al.
(författare)
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Calcium Signaling in T Cells Is Induced by Binding to Nickel-Chelating Lipids in Supported Lipid Bilayers
- 2021
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Ingår i: Frontiers in Physiology. - : Frontiers Media SA. - 1664-042X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Supported lipid bilayers (SLBs) are one of the most common cell-membrane model systems to study cell-cell interactions. Nickel-chelating lipids are frequently used to functionalize the SLB with polyhistidine-tagged ligands. We show here that these lipids by themselves can induce calcium signaling in T cells, also when having protein ligands on the SLB. This is important to avoid “false” signaling events in cell studies with SLBs, but also to better understand the molecular mechanisms involved in T-cell signaling. Jurkat T cells transfected with the non-signaling molecule rat CD48 were found to bind to ligand-free SLBs containing ≥2 wt% nickel-chelating lipids upon which calcium signaling was induced. This signaling fraction steadily increased from 24 to 60% when increasing the amount of nickel-chelating lipids from 2 to 10 wt%. Both the signaling fraction and signaling time did not change significantly compared to ligand-free SLBs when adding the CD48-ligand rat CD2 to the SLB. Blocking the SLB with bovine serum albumin reduced the signaling fraction to 11%, while preserving CD2 binding and the exclusion of the phosphatase CD45 from the cell-SLB contacts. Thus, CD45 exclusion alone was not sufficient to result in calcium signaling. In addition, more cells signaled on ligand-free SLBs with copper-chelating lipids instead of nickel-chelating lipids and the signaling was found to be predominantly via T-cell receptor (TCR) triggering. Hence, it is possible that the nickel-chelating lipids act as ligands to the cell’s TCRs, an interaction that needs to be blocked to avoid unwanted cell activation.
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| 10. |
- Dam, Tommy, et al.
(författare)
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Fluorescence-Based Measurements of Two-Dimensional Affinity in Membrane Interfaces
- 2023
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Ingår i: Methods in Molecular Biology. - 1940-6029 .- 1064-3745. ; 2654, s. 25-40
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Bokkapitel (refereegranskat)abstract
- Binding between ligands and receptors across cell contacts influences a range of biological processes including the formation of the immune synapse. The dissociation constant (Kd = 1/affinity) of the interaction corresponds to the concentration of ligands where half of the receptors in the contact have bound a ligand. In this chapter, we outline how to measure this two-dimensional affinity using model cell membranes called supported lipid bilayers (SLBs) functionalized with fluorescently labeled ligands that bind to cells containing the corresponding receptor. The affinity is calculated from the accumulation of ligands at the cell-SLB interface, while the use of different fluorescent tags, and/or unlabeled molecules, makes it possible to include various binding pairs in the contact to better mimic the conditions of binding in vivo.
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| 11. |
- Dam, Tommy, et al.
(författare)
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Supported Lipid Bilayers and the Study of Two-Dimensional Binding Kinetics
- 2022
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Ingår i: Frontiers in Molecular Biosciences. - : Frontiers Media SA. - 2296-889X. ; 9
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Forskningsöversikt (refereegranskat)abstract
- Binding between protein molecules on contacting cells is essential in initiating and regulating several key biological processes. In contrast to interactions between molecules in solution, these events are restricted to the two-dimensional (2D) plane of the meeting cell surfaces. However, converting between the more commonly available binding kinetics measured in solution and the so-called 2D binding kinetics has proven a complicated task since for the latter several factors other than the protein-protein interaction per se have an impact. A few important examples of these are: protein density, membrane fluctuations, force on the bond and the use of auxiliary binding molecules. The development of model membranes, and in particular supported lipid bilayers (SLBs), has made it possible to simplify the studied contact to analyze these effects and to measure 2D binding kinetics of individual protein-protein interactions. We will in this review give an overview of, and discuss, how different SLB systems have been used for this and compare different methods to measure binding kinetics in cell-SLB contacts. Typically, the SLB is functionalized with fluorescently labelled ligands whose interaction with the corresponding receptor on a binding cell can be detected. This interaction can either be studied 1) by an accumulation of ligands in the cell-SLB contact, whose magnitude depends on the density of the proteins and binding affinity of the interaction, or 2) by tracking single ligands in the SLB, which upon interaction with a receptor result in a change of motion of the diffusing ligand. The advantages and disadvantages of other methods measuring 2D binding kinetics will also be discussed and compared to the fluorescence-based methods. Although binding kinetic measurements in cell-SLB contacts have provided novel information on how ligands interact with receptors in vivo the number of these measurements is still limited. This is influenced by the complexity of the system as well as the required experimental time. Moreover, the outcome can vary significantly between studies, highlighting the necessity for continued development of methods to study 2D binding kinetics with higher precision and ease.
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| 12. |
- Ekström, Elin, et al.
(författare)
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WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells
- 2014
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Ingår i: Molecular Cancer. - : Springer Science and Business Media LLC. - 1476-4598. ; 13
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Tidskriftsartikel (refereegranskat)abstract
- Background: Wnt proteins are important for developmental processes and certain diseases. WNT5A is a non-canonical Wnt protein that previously has been shown to play a role in the progression of malignant melanoma. High expression of WNT5A in melanoma tumors correlates to formation of distant metastasis and poor prognosis. This has partly been described by the findings that WNT5A expression in melanoma cell lines increases migration and invasion. Methods: Malignant melanoma cell lines were treated with rWNT5A or WNT5A siRNA, and mRNA versus protein levels of soluble mediators were measured using RT-PCR, cytokine bead array and ELISA. The induced signaling pathways were analyzed using inhibitors, Rho-GTPase pull down assays and western blot. Ultracentrifugation and electron microscopy was used to analyze microvesicles. Gene expression microarray data obtained from primary malignant melanomas was used to verify our data. Results: We show that WNT5A signaling induces a Ca2+-dependent release of exosomes containing the immunomodulatory and pro-angiogenic proteins IL-6, VEGF and MMP2 in melanoma cells. The process was independent of the transcriptional machinery and depletion of WNT5A reduced the levels of the exosome-derived proteins. The WNT5A induced exosomal secretion was neither affected by Tetanus toxin nor Brefeldin A, but was blocked by the calcium chelator Bapta, inhibited by a dominant negative version of the small Rho-GTPase Cdc42 and was accompanied by cytoskeletal reorganization. Co-cultures of melanoma/endothelial cells showed that depletion of WNT5A in melanoma cells decreased endothelial cell branching, while stimulation of endothelial cells with isolated rWNT5A-induced melanoma exosomes increased endothelial cell branching in vitro. Finally, gene expression data analysis of primary malignant melanomas revealed a correlation between WNT5A expression and the angiogenesis marker ESAM. Conclusions: These data indicate that WNT5A has a broader function on tumor progression and metastatic spread than previously known; by inducing exosome-release of immunomodulatory and pro-angiogenic factors that enhance the immunosuppressive and angiogenic capacity of the tumors thus rendering them more aggressive and more prone to metastasize.
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| 13. |
- Erlandsson, Martin, et al.
(författare)
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Digital produktinformation baserat på datamallar : KONCEPTTEST MED MILJÖVARUDEKLARATIONER (EPD) OCH PRESTANDADEKLARATIONER (DOP) I WEBBTJÄNSTER (API)
- 2022
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- I framtiden måste vi bestämma oss för hur vi på ett rationellt, kvalitetssäkrat och digitalt sätt ska hantera produktinformation i byggsektorn. Visionen är att basera harmoniserad digital kvalitetsäkrad produktinformation på en internationellt användbar datamall.Grunderna för digitala datamallar och hur de tas fram beskrivs i standarderna ISO 23386/7 och ISO 23387.En ifylld datamall kallas ett datablad. I det här genomförda tillämpningstestet (proof of concept, PoC) av datamallar är syftet att kommunicera produktinformation digitalt i värdekedjan från materialtillverkan till dess att byggprodukten levererats till byggarbetsplatsen.I tillämpningstestet ingår flera materiatillverkare som har varit testpiloter för att ta fram datablad enligt datamalls-konceptet. Piloterna har tagit fram datablad för prestandadeklarationen (DoP) som är kopplat till produktens CE-märkning, samt för en EPD baserat på den globala datamallen som beskrivs i standarden ISO 22057.
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| 14. |
- Fontes Villalba, Maelan, et al.
(författare)
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A healthy diet with and without cereal grains and dairy products in patients with type 2 diabetes: study protocol for a random-order cross-over pilot study - Alimentation and Diabetes in Lanzarote -ADILAN.
- 2014
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Ingår i: Trials. - : Springer Science and Business Media LLC. - 1745-6215. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Research on the role of nutrition in type 2 diabetes has largely focused on macro/micronutrient composition and dietary fiber intake, while fewer studies have tested the effects of differing food choice. Some observational studies and short-term intervention studies suggest that a food pattern mimicking the diet with which humans evolved positively influences glucose control and associated endocrine systems. Such a food pattern mainly differs from other common healthy food patterns in its absence of cereal grains and dairy products. The primary aim of this pilot study is to determine the effect of two healthy diets with or without cereal grains and dairy products on glucose control, while keeping participants' weight stable and other food parameters, such as macro/micronutrient composition, dietary fiber and glycemic load, the same in both diets.
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| 15. |
- Fontes-Villalba, Maelán, et al.
(författare)
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Palaeolithic diet decreases fasting plasma leptin concentrations more than a diabetes diet in patients with type 2 diabetes : A randomised cross-over trial
- 2016
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Background: We have previously shown that a Palaeolithic diet consisting of the typical food groups that our ancestors ate during the Palaeolithic era, improves cardiovascular disease risk factors and glucose control compared to the currently recommended diabetes diet in patients with type 2 diabetes. To elucidate the mechanisms behind these effects, we evaluated fasting plasma concentrations of glucagon, insulin, incretins, ghrelin, C-peptide and adipokines from the same study. Methods: In a randomised, open-label, cross-over study, 13 patients with type 2 diabetes were randomly assigned to eat a Palaeolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts, or a diabetes diet designed in accordance with current diabetes dietary guidelines during two consecutive 3-month periods. The patients were recruited from primary health-care units and included three women and 10 men [age (mean ± SD) 64 ± 6 years; BMI 30 ± 7 kg/m2; diabetes duration 8 ± 5 years; glycated haemoglobin 6.6 ± 0.6 % (57.3 ± 6 mmol/mol)] with unaltered diabetes treatment and stable body weight for 3 months prior to the start of the study. Outcome variables included fasting plasma concentrations of leptin, adiponectin, adipsin, visfatin, resistin, glucagon, insulin, C-peptide, glucose-dependent insulinotropic polypeptide, glucagon-like peptide-1 and ghrelin. Dietary intake was evaluated by use of 4-day weighed food records. Results: Seven participants started with the Palaeolithic diet and six with the diabetes diet. The Palaeolithic diet resulted in a large effect size (Cohen's d = -1.26) at lowering fasting plasma leptin levels compared to the diabetes diet [mean difference (95 % CI), -2.3 (-5.1 to 0.4) ng/ml, p = 0.023]. No statistically significant differences between the diets for the other variables, analysed in this study, were observed. Conclusions: Over a 3-month study period, a Palaeolithic diet resulted in reduced fasting plasma leptin levels, but did not change fasting levels of insulin, C-peptide, glucagon, incretins, ghrelin and adipokines compared to the currently recommended diabetes diet. Trial registration: Clinical Trials.gov NCT00435240.
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| 16. |
- Goldenberg, Joshua Z., et al.
(författare)
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Efficacy and safety of low and very low carbohydrate diets for type 2 diabetes remission : systematic review and meta-analysis of published and unpublished randomized trial data
- 2021
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Ingår i: BMJ (Clinical research ed.). - : BMJ. - 1756-1833. ; 372
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To determine the efficacy and safety of low carbohydrate diets (LCDs) and very low carbohydrate diets (VLCDs) for people with type 2 diabetes. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Searches of CENTRAL, Medline, Embase, CINAHL, CAB, and grey literature sources from inception to 25 August 2020. STUDY SELECTION: Randomized clinical trials evaluating LCDs (<130 g/day or <26% of a 2000 kcal/day diet) and VLCDs (<10% calories from carbohydrates) for at least 12 weeks in adults with type 2 diabetes were eligible. DATA EXTRACTION: Primary outcomes were remission of diabetes (HbA1c <6.5% or fasting glucose <7.0 mmol/L, with or without the use of diabetes medication), weight loss, HbA1c, fasting glucose, and adverse events. Secondary outcomes included health related quality of life and biochemical laboratory data. All articles and outcomes were independently screened, extracted, and assessed for risk of bias and GRADE certainty of evidence at six and 12 month follow-up. Risk estimates and 95% confidence intervals were calculated using random effects meta-analysis. Outcomes were assessed according to a priori determined minimal important differences to determine clinical importance, and heterogeneity was investigated on the basis of risk of bias and seven a priori subgroups. Any subgroup effects with a statistically significant test of interaction were subjected to a five point credibility checklist. RESULTS: Searches identified 14 759 citations yielding 23 trials (1357 participants), and 40.6% of outcomes were judged to be at low risk of bias. At six months, compared with control diets, LCDs achieved higher rates of diabetes remission (defined as HbA1c <6.5%) (76/133 (57%) v 41/131 (31%); risk difference 0.32, 95% confidence interval 0.17 to 0.47; 8 studies, n=264, I2=58%). Conversely, smaller, non-significant effect sizes occurred when a remission definition of HbA1c <6.5% without medication was used. Subgroup assessments determined as meeting credibility criteria indicated that remission with LCDs markedly decreased in studies that included patients using insulin. At 12 months, data on remission were sparse, ranging from a small effect to a trivial increased risk of diabetes. Large clinically important improvements were seen in weight loss, triglycerides, and insulin sensitivity at six months, which diminished at 12 months. On the basis of subgroup assessments deemed credible, VLCDs were less effective than less restrictive LCDs for weight loss at six months. However, this effect was explained by diet adherence. That is, among highly adherent patients on VLCDs, a clinically important reduction in weight was seen compared with studies with less adherent patients on VLCDs. Participants experienced no significant difference in quality of life at six months but did experience clinically important, but not statistically significant, worsening of quality of life and low density lipoprotein cholesterol at 12 months. Otherwise, no significant or clinically important between group differences were found in terms of adverse events or blood lipids at six and 12 months. CONCLUSIONS: On the basis of moderate to low certainty evidence, patients adhering to an LCD for six months may experience remission of diabetes without adverse consequences. Limitations include continued debate around what constitutes remission of diabetes, as well as the efficacy, safety, and dietary satisfaction of longer term LCDs. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020161795.
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| 17. |
- Guidetti, Roberto, et al.
(författare)
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Diversity of the tardigrade communities in the Norwegian forests
- 2022
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Konferensbidrag (refereegranskat)abstract
- Background: Tardigrades are common in most habitats, however few studies have focused on large faunistic survey, specifically on tardigrade diversity in forests. Up to now, only 61 species have been recorded in different types of forest in Norway with an additional 25 found in limnic environments in forests. Although little is known about the ecological preferences of many species, previous studies have found that tardigrade diversity and community composition are significantly affected by ecological variables. In this study we associate georeferenced tardigrade species records with forest type, substrate type and substrate composition in order to see if tardigrade diversity and species communities can be associated with ecological characteristics of Norwegian forests. Methods: In total 390 moss, lichen and litter samples were collected from 12 forests in central and southern Norway in the summers of 2017 and 2018 and later stored in paper envelopes. For the identification modern literature and keys forspecific genera and groups of species were used. For statistical analyses, moss and lichen substrate of each sample was classified according to the main species, life form, growth forms and habitat of substrate and associated with each tardigrade identification and sample metadata. Results: A total of 17 407 specimens were identified, encompassing in total 132 species (including some new species). Species richness increases with precipitation, but does not change with temperature or precipitation seasonality. The distribution of species richness between life forms and forest types showed considerable variation within and among the variables. Disregarding variables with low sample numbers, among life forms only acrocarpous moss samples appeared to deviate with respect to species richness, containing less species than substrates with other life forms. Conclusions: Tardigrades in Norwegian forest are extremely abundant, frequent and diverse. Moreover, it appears that that certain species and/or entirecommunities prefer specific microhabitats.
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| 18. |
- Guidetti, Roberto, et al.
(författare)
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Tardigrade diversity and community composition across Norwegian boreal forests
- 2023
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Ingår i: Zoological Journal of the Linnean Society. - : Oxford University Press. - 0024-4082 .- 1096-3642.
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Tidskriftsartikel (refereegranskat)abstract
- Tardigrades are common in many terrestrial environments and habitats. Although little is known on their ecological preferences, previous studies found diversity and community composition significantly affected by various variables. This study associated tardigrade species’ records with climatic variables, forest type, and substrate categories exploring tardigrade diversity and species communities to find associations with ecological characteristics of Norwegian forests. A total of 17 473 specimens were identified, encompassing 131 species (including putatively new species) from 305 samples of different substrates (leaf litter, bryophytes, and lichens). Bryophytes and lichens of samples were classified according to the main species, and growth form, and associated with tardigrade species and sample metadata. Tardigrade species’ richness was related to climatic variables and forest type, increased with precipitation, decreased with summer temperature, and not varied with precipitation seasonality. Although there was an unbalanced representation of substrate categories in the different forest types, some tendencies were detectable. Mixed oak and birch forests reached the highest species’ richness. Tardigrade community composition varied between substrate categories and, to a lesser degree, between forest types, but not with climatic variables. Our study highlights the importance of large-scale variables on tardigrade diversity, and substrate categories for tardigrade community composition.
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| 19. |
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| 20. |
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| 21. |
- Junghans, Victoria, et al.
(författare)
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Effects of a local auxiliary protein on the two-dimensional affinity of a TCR-peptide MHC interaction
- 2020
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Ingår i: Journal of Cell Science. - : The Company of Biologists Ltd.. - 0021-9533 .- 1477-9137. ; 133:15
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Tidskriftsartikel (refereegranskat)abstract
- The affinity of T-cell receptors (TCRs) for major histocompatibility complex molecules (MHCs) presenting cognate antigens likely determines whether T cells initiate immune responses, or not. There exist few measurements of two-dimensional (2D) TCR-MHC interactions, and the effect of auxiliary proteins on binding is unexplored. Here, Jurkat T-cells expressing the MHC molecule HLA-DQ8-glia-α1 and the ligand of an adhesion protein (rat CD2) were allowed to bind supported lipid bilayers (SLBs) presenting fluorescently-labelled L3-12 TCR and rat CD2, allowing measurements of binding unconfounded by cell signaling effects or co-receptor binding. The 2D Kd for L3-12 TCR binding to HLA-DQ8-glia-α1, 14±5 molecules/μm2, was only marginally influenced by including CD2 up to ∼200 bound molecules/μm2 but higher CD2 densities reduced the affinity up to 1.9-fold. Cell-SLB contact size increased steadily with ligand density without affecting binding for contacts up to ∼20% of total cell area but beyond this lamellipodia appeared, giving an apparent increase in bound receptors of up to 50%. Our findings show how parameters other than the specific protein-protein interaction can influence binding behavior at cell-cell contacts.
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| 22. |
- Jönsson, Björn, 1951-, et al.
(författare)
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A new probe for ankle systolic pressure measurement using Photoplethysmography (PPG)
- 2005
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Ingår i: Annals of Biomedical Engineering. - : Springer Science and Business Media LLC. - 0090-6964 .- 1573-9686. ; 33:2, s. 232-239
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Tidskriftsartikel (refereegranskat)abstract
- An automated method for ankle systolic pressure measurement, less operator dependent than the standard continuous wave (CW) Doppler technique, would imply an advantage both in patient measurements and in epidemiological studies. We present a new photoplethysmographic (PPG) probe that uses near-infrared light (880 nm) to detect pulsatory blood flow underneath the distal end of a standard pneumatic cuff. The probe is adapted to the anatomical conditions at the ankle, permitting recording of pressures in both ankle arteries separately. The validity of the equipment was tested with CW Doppler-derived systolic pressures and invasive blood pressure measurements for reference. In 20 healthy subjects, visual analysis of the PPG curves revealed a mean difference between CW Doppler and PPG measurements of –0.5 mmHg (SD 6.9). Corresponding results for the anterior and posterior tibial arteries separately were –1.8 mmHg (SD 6.2) and 0.9 mmHg (SD 7.3), respectively. A correct probe position was essential for the results. In direct recordings from the dorsalis pedis artery in 10 intensive care patients, PPG underestimated systolic pressure in the anterior tibial artery by 4.5 mmHg (SD 12.1). With further development, the PPG probe, integrated in the pneumatic cuff, may simplify measurements of ankle systolic pressures.
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| 23. |
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| 24. |
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| 25. |
- Jönsson, Björn, 1951-, et al.
(författare)
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Ankle-brachial index and mortality in a cohort of questionnaire recorded leg pain on walking
- 2002
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 24:5, s. 405-410
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Tidskriftsartikel (refereegranskat)abstract
- Objective: to study the association between the ankle–brachial pressure index (ABPI), premature death and the need for surgical treatment for lower limb ischaemia.Design: population based cohort study.Subjects: three hundred and fifty-three men and women, 50–89 years old, underwent a leg pain questionnaire and measurement of ABPI and was then followed for 10 years.Outcome Measures: all cause mortality, vascular procedures and major amputations.Results: a low ABPI was independently associated with premature all cause mortality in the multiple regression analysis, carrying a relative risk of 3.4 (95% confidence interval 2.0–5.9) and 2.1 (1.3–3.3) for ABPIs ≤0.50 and 0.51–0.80, respectively, compared to those with ABPI ≥1.0. Individuals with an ABPI in the interval 0.81–0.99 suffered only a slight, not statistically significant risk increase compared to normals. A low ABPI at baseline implied a continuous constant increased risk of death throughout the study period. The same risk was observed among elderly (70–89, median 77 years), and in the middle aged (50–69, median 63 years) individuals. The vast majority of those subjected to vascular intervention or major amputation during follow-up had an ABPI≤0.8 at baseline (83 and 89%, respectively). However, within that group, the individual ABPI was not predictive for surgical intervention.Conclusion: the association found between an ABPI ≤0.8 and premature mortality in this cohort of symptomatic subjects implies that the ABPI is a powerful, independent predictor for premature death. The prognostic information carried by an ABPI in the interval 0.81–0.99 remains uncertain. Septuagenarians and octogenarians carry the same risk increase associated with a low ABPI as those in the middle ages.
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| 26. |
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| 27. |
- Jönsson, Björn, 1951-, et al.
(författare)
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Automatic ankle pressure measurements using PPG in ankle-brachial pressure index determination
- 2005
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Ingår i: European Journal of Vascular and Endovascular Surgery. - : Elsevier BV. - 1078-5884 .- 1532-2165. ; 30:4, s. 395-401
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Tidskriftsartikel (refereegranskat)abstract
- ObjectiveTo evaluate a new technique using a photoplethysmographic (PPG) probe for automatic ankle pressure measurements.DesignComparative study on two techniques for ankle pressure measurement.SettingUniversity hospital.MaterialThirty-five patients with leg arterial disease and eight healthy volunteers. Ankle-brachial indices (ABPI) were measured using conventional CW Doppler technique and PPG-based prototype equipment for the ankle pressure recordings.Chief outcome measuresABPIs calculated from CW Doppler and PPG ankle pressure measurements. The PPG signals were analysed both by visual judgement and by a software based, automatic algorithm.Main resultsThe mean difference between ABPIs calculated from CW Doppler recordings and PPG (visual analysis) was −0.01 (limits of agreement (±two standard deviations) +0.16 to −0.19). The correlation coefficient was 0.93. When the algorithm was used, the mean difference (CW Doppler−PPG) was 0.05 (limits of agreement 0.28 to −0.18, r=0.89).ConclusionsThe PPG method is a promising technique with an inherent potential for automatisation of the ankle pressure measurements, thereby reducing the observer-dependency in ABPI recordings.
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| 28. |
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| 29. |
- Jönsson, Björn, 1951-, et al.
(författare)
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Is oscillometric ankle pressure reliable in leg vascular disease?
- 2001
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Ingår i: Clinical Physiology and Functional Imaging. - : Wiley. - 1475-0961 .- 1475-097X. ; 21:2, s. 155-163
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Tidskriftsartikel (refereegranskat)abstract
- The objective of the study was to evaluate the validity of oscillometric systolic ankle pressure in symptomatic leg arterial occlusive disease. Ankle pressure measurements using oscillometric curves obtained using a standard 12-cm cuff with a specially designed device for signal processing were validated against the continuous wave (CW) Doppler technique. Thirty-four subjects without signs or symptoms of peripheral vascular disease (68 legs) and 47 patients with leg ischaemia (85 legs) varying from moderate claudication to critical ischaemia were examined. The oscillometric curves were analysed using several algorithms reported in the literature, based on the assumption that maximum oscillations are recorded near mean arterial pressure. In normals, reasonable agreement between CW Doppler and oscillometric methods was seen. When an algorithm that determined the lowest cuff pressure at which maximum oscillations occurred, and a characteristic ratio for systolic pressure of 0·52 was used, the mean difference between CW Doppler and oscillometry was 1·7 mmHg [range −19 to +27, limits of agreement (2 SD) 21·1 mmHg]. In ischaemic legs, oscillometry overestimated systolic ankle pressure by a mean of 28·8 mmHg [range –126 to +65, limits of agreement 82·8 mmHg]. The difference was more pronounced among patients with critical ischaemia compared with claudicants, and also more evident among diabetics. The error of oscillometric pressure determination in subjects with leg arterial disease inversely increased with CW Doppler ankle pressure. In 39% of the recordings in legs with a CW Doppler systolic pressure below 100 mmHg, the oscillometric mean arterial pressure was higher than the recorded CW Doppler systolic pressure. In conclusion, the oscillometric method to determine systolic ankle pressure, based on the concept of maximum cuff oscillations occurring near mean arterial pressure, is not reliable in leg arterial disease, usually overestimating ankle pressure.
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| 30. |
- Jönsson, Björn, et al.
(författare)
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Outcome of symptomatic leg ischaemia : four year morbidity and mortality in vadstena, Sweden
- 1996
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Ingår i: European Journal of Vascular and Endovascular Surgery. - 1078-5884 .- 1532-2165. ; 11:3, s. 315-232
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Tidskriftsartikel (refereegranskat)abstract
- Objective:To quantify cardiovascular morbidity and mortality including the incidence of vascular surgery and amputations, among individuals with symptomatic leg ischaemia.Design:Prospective cohort study.Material:Inhabitants 50–89 years of age (n = 2784) of Vadstena community, Östergötland, Sweden, with 4 years of follow-up. 107 subjects with symptomatic leg ischaemia (SLI), selected by a postal questionnaire and ankle pressure measurements, and an age and sex matched control group of 214 individuals.Chief outcome measures:Cardiovascular morbidity and mortality, all cause mortality, surgical procedures for leg ischaemia, major amputations, ankle brachial pressure index.Main results:Age and sex adjusted all-cause mortality risk in the SLI-group was increased by 1.9. This was most prominent among men in their sixties and women in their seventies. Cardiovascular mortality was increased by 1.9 (95% confidence interval 1.1–3.3). Relative risks for acute myocardial infarction and cerebrovascular events were 2.4 (1.1–5.1) and 1.7 (0.9–3.2), respectively. The increase in age and sex adjusted incidence of primary reconstructive surgery during the first year after initial examination was 67-fold compared to the total population of Vadstena 50–89 years old, and 18-fold for the whole observation period, while the increase in risk for major amputation during the observation period was 12-fold. Median ankle brachial index improved significantly during follow-up among the individuals alive and not subjected to vascular surgery.Conclusions:Among the SLI-subjects identified in a general population, the overall risk for cardiovascular morbidity and mortality over 4 years was significantly increased compared to normals.
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| 31. |
- Jönsson, Christer, et al.
(författare)
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Studying Diplomacy
- 2006
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Ingår i: Diplomacy and Psychology: Prevention of Armed Conflicts after the Cold War. ; , s. 43-57
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter singles out three areas of possible future research, where psychology in collaboration with other social science disciplines may make important contributions: (1) diplomatic signaling, (2) diplomatic culture, and (3) interaction dynamics.
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| 32. |
- Jönsson, Marzieh, et al.
(författare)
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Loss of Wnt-5a protein is associated with early relapse in invasive ductal breast carcinomas.
- 2002
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Ingår i: Cancer Research. - 1538-7445. ; 62:2, s. 409-416
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Tidskriftsartikel (refereegranskat)abstract
- Previous in vitro studies have implied that the Wnt-5a gene plays a role as a tumor suppressor. To explore the clinical relevance of this concept, 96 primary invasive breast carcinomas were stained with a novel anti-Wnt-5a antibody. Loss of Wnt-5a protein expression, evident in 44% of the invasive ductal carcinomas (n = 59), was significantly associated with higher histological grade (P = 0.01) and absence of estrogen (P = 0.003) and progesterone (P = 0.02) receptors. By contrast, loss of Wnt-5a protein in 24% of the invasive lobular carcinomas (n = 37) was not significantly related to any of the variables we investigated. The prognostic value of Wnt-5a for metastatic potential was evaluated by analyzing 83 additional invasive primary ductal carcinomas from patients with a longer follow-up time. We found that Wnt-5a expression was lost in tumors from 78% of the patients with recurrent disease (n = 32) compared with 35% of the recurrence-free patients (n = 51; P < 0.001), and that recurrence-free survival was significantly shorter in the Wnt-5a-negative group (P < 0.001). In multivariate analyses, loss of Wnt-5a expression proved to be an independent and powerful predictor of recurrence after adjustment for lymph node status and tumor size (hazard ratio = 4.8; P = 0.002). Our results show that loss of Wnt-5a increases the risk of early relapse and death because of recurrent ductal breast cancer, findings that support the notion that this protein retains tumor suppressor function by virtue of its effects on cell adhesion and motility.
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| 33. |
- Jönsson, Marzieh, et al.
(författare)
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Repression of Wnt-5a impairs DDR1 phosphorylation and modifies adhesion and migration of mammary cells
- 2001
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Ingår i: Journal of Cell Science. - 0021-9533. ; 114:Pt 11, s. 2043-2053
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Tidskriftsartikel (refereegranskat)abstract
- The Wnt-5a gene encodes a secreted protein that controls several normal processes during embryogenesis and development of adult tissues by as yet unknown mechanisms. Endogenous expression of Wnt-5a mRNA is known to occur in both mouse and human mammary cell lines. To investigate the biological role of Wnt-5a in the human mammary epithelial cell line HB2, we used an antisense approach to repress endogenous expression of Wnt-5a protein. We also generated a cell population that constitutively overexpresses this protein. We found that overexpression of Wnt-5a protein enhanced cell-to-collagen binding and abolished hepatocyte growth factor-stimulated migration of HB2 transfectants through collagen matrices. Conversely, repression of Wnt-5a protein led to cell scattering, impaired cell-collagen interaction and enhanced cell motility. As we were searching for modified collagen receptors in antisense cells, we discovered that the collagen-binding discoidin domain receptor 1 (DDR1) failed to undergo phosphorylation. In reciprocal experiments, phosphorylation of DDR1 was consistently enabled by expression of Wnt-5a-HA protein in non-Wnt-5a-producing MCF-7 breast cancer cells. Activation of the Wnt/beta-catenin signalling pathway did not influence or mimic the Wnt-5a-mediated effect on DDR1 phosphorylation. These data demonstrate that Wnt-5a protein participates in regulation of adhesion to and migration through collagen and is also a co-factor necessary for collagen-induced activation of DDR1 receptors in mammary epithelial cells.
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| 34. |
- Jönsson, Tommy, et al.
(författare)
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A Paleolithic diet confers higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet in domestic pigs.
- 2006
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Ingår i: Nutrition & Metabolism. - : Springer Science and Business Media LLC. - 1743-7075. ; 3:Article nr. 39
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Tidskriftsartikel (refereegranskat)abstract
- A Paleolithic diet has been suggested to be more in concordance with human evolutionary legacy than a cereal based diet. This might explain the lower incidence among hunter-gatherers of diseases of affluence such as type 2 diabetes, obesity and cardiovascular disease. The aim of this study was to experimentally study the long-term effect of a Paleolithic diet on risk factors for these diseases in domestic pigs. We examined glucose tolerance, post-challenge insulin response, plasma C-reactive protein and blood pressure after 15 months on Paleolithic diet in comparison with a cereal based swine feed.
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| 35. |
- Jönsson, Tommy, et al.
(författare)
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A paleolithic diet is more satiating per calorie than a mediterranean-like diet in individuals with ischemic heart disease.
- 2010
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Ingår i: Nutrition & Metabolism. - : Springer Science and Business Media LLC. - 1743-7075. ; 7, s. 85-99
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Tidskriftsartikel (refereegranskat)abstract
- We found marked improvement of glucose tolerance and lower dietary energy intake in ischemic heart disease (IHD) patients after advice to follow a Paleolithic diet, as compared to a Mediterranean-like diet. We now report findings on subjective ratings of satiety at meals and data on the satiety hormone leptin and the soluble leptin receptor from the same study.
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| 36. |
- Jönsson, Tommy, et al.
(författare)
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Agrarian diet and diseases of affluence--do evolutionary novel dietary lectins cause leptin resistance?
- 2005
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Ingår i: BMC Endocrine Disorders. - : Springer Science and Business Media LLC. - 1472-6823. ; 5:10
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The global pattern of varying prevalence of diseases of affluence, such as obesity, cardiovascular disease and diabetes, suggests that some environmental factor specific to agrarian societies could initiate these diseases. PRESENTATION OF THE HYPOTHESIS: We propose that a cereal-based diet could be such an environmental factor. Through previous studies in archaeology and molecular evolution we conclude that humans and the human leptin system are not specifically adapted to a cereal-based diet, and that leptin resistance associated with diseases of affluence could be a sign of insufficient adaptation to such a diet. We further propose lectins as a cereal constituent with sufficient properties to cause leptin resistance, either through effects on metabolism central to the proper functions of the leptin system, and/or directly through binding to human leptin or human leptin receptor, thereby affecting the function. TESTING THE HYPOTHESIS: Dietary interventions should compare effects of agrarian and non-agrarian diets on incidence of diseases of affluence, related risk factors and leptin resistance. A non-significant (p = 0.10) increase of cardiovascular mortality was noted in patients advised to eat more whole-grain cereals. Our lab conducted a study on 24 domestic pigs in which a cereal-free hunter-gatherer diet promoted significantly higher insulin sensitivity, lower diastolic blood pressure and lower C-reactive protein as compared to a cereal-based swine feed. Testing should also evaluate the effects of grass lectins on the leptin system in vivo by diet interventions, and in vitro in various leptin and leptin receptor models. Our group currently conducts such studies. IMPLICATIONS OF THE HYPOTHESIS: If an agrarian diet initiates diseases of affluence it should be possible to identify the responsible constituents and modify or remove them so as to make an agrarian diet healthier.
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| 37. |
- Jönsson, Tommy, et al.
(författare)
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Beneficial effects of a Paleolithic diet on cardiovascular risk factors in type 2 diabetes: a randomized cross-over pilot study
- 2009
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Ingår i: Cardiovascular Diabetology. - : Springer Science and Business Media LLC. - 1475-2840. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Background: Our aim was to compare the effects of a Paleolithic ('Old Stone Age') diet and a diabetes diet as generally recommended on risk factors for cardiovascular disease in patients with type 2 diabetes not treated with insulin. Methods: In a randomized cross-over study, 13 patients with type 2 diabetes, 3 women and 10 men, were instructed to eat a Paleolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; and a Diabetes diet designed in accordance with dietary guidelines during two consecutive 3-month periods. Outcome variables included changes in weight, waist circumference, serum lipids, C-reactive protein, blood pressure, glycated haemoglobin (HbA1c), and areas under the curve for plasma glucose and plasma insulin in the 75 g oral glucose tolerance test. Dietary intake was evaluated by use of 4-day weighed food records. Results: Study participants had on average a diabetes duration of 9 years, a mean HbA1c of 6,6% units by MonoS standard and were usually treated with metformin alone (3 subjects) or metformin in combination with a sulfonylurea (3 subjects) or a thiazolidinedione (3 subjects). Mean average dose of metformin was 1031 mg per day. Compared to the diabetes diet, the Paleolithic diet resulted in lower mean values of HbA1c (-0.4% units, p = 0.01), triacylglycerol (-0.4 mmol/L, p = 0.003), diastolic blood pressure (-4 mmHg, p = 0.03), weight (-3 kg, p = 0.01), BMI (-1 kg/m(2), p = 0.04) and waist circumference (-4 cm, p = 0.02), and higher mean values of high density lipoprotein cholesterol (+0.08 mmol/L, p = 0.03). The Paleolithic diet was mainly lower in cereals and dairy products, and higher in fruits, vegetables, meat and eggs, as compared with the Diabetes diet. Further, the Paleolithic diet was lower in total energy, energy density, carbohydrate, dietary glycemic load, saturated fatty acids and calcium, and higher in unsaturated fatty acids, dietary cholesterol and several vitamins. Dietary GI was slightly lower in the Paleolithic diet (GI = 50) than in the Diabetic diet (GI = 55). Conclusion: Over a 3-month study period, a Paleolithic diet improved glycemic control and several cardiovascular risk factors compared to a Diabetes diet in patients with type 2 diabetes.
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| 38. |
- Jönsson, Tommy, et al.
(författare)
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Digested wheat gluten inhibits binding between leptin and its receptor
- 2015
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Ingår i: BMC Biochemistry. - : Springer Science and Business Media LLC. - 1471-2091. ; 16
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Tidskriftsartikel (refereegranskat)abstract
- Background: Leptin resistance is considered a primary risk factor for obesity. It has been hypothesized that dietary cereal grain protein could cause leptin resistance by preventing leptin from binding to its receptor. Non-degraded dietary wheat protein has been found in human serum at a mean level of 41 ng/mL. Here, we report our findings from testing whether enzymatically digested gluten from wheat prevents leptin from binding to the leptin receptor in vitro. Gluten from wheat was digested with pepsin and trypsin under physiological conditions. Pepsin and trypsin activity was removed from the gluten digest with a 10 kDa spin-filter or by heat treatment at 100 degrees C for 30 min. Binding to the leptin receptor of leptin mixed with gluten digest at a series of concentrations was measured using surface plasmon resonance technology. Results: Binding of the gluten digest to the leptin receptor was not detected. Spin-filtered gluten digest inhibited binding of leptin to the leptin receptor, with 50% inhibition at a gluten digest concentration of similar to 10 ng/mL. Heat-treated gluten digest did not inhibit leptin binding. Conclusions: Digested wheat gluten inhibits binding of leptin to the leptin receptor, with half-maximal inhibition at 10 ng/mL. The inhibition is significant at clinically relevant concentrations and could therefore serve as a novel pathway to investigate to understand the molecular basis of leptin resistance, obesity and associated disorders.
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| 39. |
- Jönsson, Tommy
(författare)
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Healthy Satiety Effects of Paleolithic diet on Satiety and Risk factors for Cardiovascular disease
- 2007
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- The prevalence of cardiovascular diseases (CVD) exhibits considerable variation across agrarian societies, whereas they are virtually absent in non-agrarian societies such as hunter-gatherer and horticultural societies. When looking for lifestyle factors which could promote CVD, it therefore seems logical to focus on the agrarian lifestyle and ways in which it departs from a non-agrarian lifestyle. The aim of this thesis was to evaluate the effect of a hunter-gatherer diet (also called Paleolithic diet) compared to agrarian diet in prevention of CVD. In paper I we reviewed evidence from epidemiology and evolutionary biology for a possible maladaptation of human satiety hormone leptin to agrarian diet. We found that leptin resistance hypothetically may be a sign of maladaptation to dietary cereals as staple food, and that lectins could be a cereal constituent with sufficient properties to cause leptin resistance. In paper II we experimentally studied the long-term effect of a Paleolithic diet compared to a cereal-based diet on risk factors for cardiovascular disease in domestic pigs. We found that a Paleolithic diet conferred higher insulin sensitivity, lower C-reactive protein and lower blood pressure than a cereal-based diet. In paper III and IV we experimentally studied the effect of a Paleolithic diet compared to a Mediterranean-like diet on risk factors for cardiovascular disease, satiety and leptin in individuals with ischaemic heart disease and either glucose intolerance or type 2 diabetes. Paper III showed that a Paleolithic diet improved glucose tolerance more than a Mediterranean-like diet, and paper IV showed that a Paleolithic diet was more satiating per calorie than a Mediterranean-like diet. In conclusion, we have found beneficial effects of a Paleolithic diet on risk factors for cardiovascular disease and satiety.
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| 40. |
- Jönsson, Tommy, et al.
(författare)
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Subjective satiety and other experiences of a Paleolithic diet compared to a diabetes diet in patients with type 2 diabetes
- 2013
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Ingår i: Nutrition Journal. - : Springer Science and Business Media LLC. - 1475-2891. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- Background: We found marked improvement of glycemic control and several cardiovascular risk factors in patients with type 2 diabetes given advice to follow a Paleolithic diet, as compared to a diabetes diet. We now report findings on subjective ratings of satiety at meal times and participants' other experiences of the two diets from the same study. Methods: In a randomized cross-over study, 13 patients with type 2 diabetes (3 women and 10 men), were instructed to eat a Paleolithic diet based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts, and a diabetes diet designed in accordance with dietary guidelines, during two consecutive 3-month periods. In parallel with a four-day weighed food record, the participants recorded their subjective rating of satiety. Satiety quotients were calculated as the intra-meal quotient of change in satiety during a meal and consumed energy or weight of food and drink for that specific meal. All participants answered the same three open-ended questions in a survey following each diet: "What thoughts do you have about this diet?", "Describe your positive and negative experiences with this diet" and "How do you think this diet has affected your health?". Results: The participants were equally satiated on both diets. The Paleolithic diet resulted in greater satiety quotients for energy per meal (p = 0.004), energy density per meal (p = 0.01) and glycemic load per meal (p = 0.02). The distribution of positive and negative comments from the survey did not differ between the two diets, and the comments were mostly positive. Among comments relating to recurring topics, there was no difference in distribution between the two diets for comments relating to tastelessness, but there was a trend towards more comments on the Paleolithic diet being satiating and improving blood sugar values, and significantly more comments on weight loss and difficulty adhering to the Paleolithic diet. Conclusions: A Paleolithic diet is more satiating per calorie than a diabetes diet in patients with type 2 diabetes. The Paleolithic diet was seen as instrumental in weight loss, albeit it was difficult to adhere to.
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| 41. |
- Lindeberg, Staffan, et al.
(författare)
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A Palaeolithic diet improves glucose tolerance more than a Mediterranean-like diet in individuals with ischaemic heart disease.
- 2007
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 1432-0428 .- 0012-186X. ; 50:9, s. 1795-1807
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Tidskriftsartikel (refereegranskat)abstract
- Aims/hypothesis Most studies of diet in glucose intolerance and type 2 diabetes have focused on intakes of fat, carbohydrate, fibre, fruits and vegetables. Instead, we aimed to compare diets that were available during human evolution with more recently introduced ones. Methods Twenty-nine patients with ischaemic heart disease plus either glucose intolerance or type 2 diabetes were randomised to receive (1) a Palaeolithic ('CyOld Stone Age') diet (n=14), based on lean meat, fish, fruits, vegetables, root vegetables, eggs and nuts; or (2) a Consensus (Mediterranean-like) diet (n=15), based on whole grains, low-fat dairy products, vegetables, fruits, fish, oils and margarines. Primary outcome variables were changes in weight, waist circumference and plasma glucose AUC (AUC Glucose(0-120)) and plasma insulin AUC (AUC Insulin(0-120)) in OGTTs. Results Over 12 weeks, there was a 26% decrease of AUC Glucose(0-120) (p=0.0001) in the Palaeolithic group and a 7% decrease (p=0.08) in the Consensus group. The larger (p=0.001) improvement in the Palaeolithic group was independent (p=0.0008) of change in waist circumference (-5.6 cm in the Palaeolithic group, -2.9 cm in the Consensus group; p=0.03). In the study population as a whole, there was no relationship between change in AUC Glucose(0-120) and changes in weight (r=-0.06, p=0.9) or waist circumference (r=0.01, p=1.0). There was a tendency for a larger decrease of AUC Insulin(0-120) in the Palaeolithic group, but because of the strong association between change in AUC Insulin(0-120) and change in waist circumference (r=0.64, p=0.0003), this did not remain after multivariate analysis. Conclusions/interpretationA Palaeolithic diet may improve glucose tolerance independently of decreased waist circumference.
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| 42. |
- Linnskog, Rickard, et al.
(författare)
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Interleukin-6 drives melanoma cell motility through p38α-MAPK-dependent up-regulation of WNT5A expression.
- 2014
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 8:8, s. 1365-1378
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Tidskriftsartikel (refereegranskat)abstract
- Extensive research has demonstrated a tumor-promoting role of increased WNT5A expression in malignant melanoma. However, very little light has been shed upon how WNT5A expression is up-regulated in melanoma. A potential regulator of WNT5A expression is the pro-inflammatory cytokine Interleukin (IL)-6, which shares the ability of WNT5A to increase melanoma cell invasion. Here, we investigate whether IL-6 can promote melanoma cell motility through an increased expression of WNT5A. We clearly demonstrate that the WNT5A-antagonistic peptide Box5 could inhibit IL-6-induced melanoma cell migration and invasion. Furthermore, IL-6 stimulation of the human melanoma cell lines HTB63 and A375 increased the expression of WNT5A in a dose-dependent manner. To identify the signaling mechanism responsible for this up-regulation, we explored the involvement of the three main signals induced by IL-6; STAT3, Akt and ERK 1/2. Of these, only STAT3 was activated by IL-6 in the melanoma cell lines tested. However, the STAT3 inhibitor S3I-201 failed to inhibit IL-6-induced WNT5A up-regulation in HTB63 and A375 cells. Nor did STAT3 siRNA silencing affect the expression of WNT5A. In search of an alternative signaling mechanism, we detected IL-6-induced activation of p38-MAPK in HTB63 and A375 cells. The p38-MAPK inhibitor SB203580 abolished the IL-6-induced WNT5A up-regulation and blocked IL-6-induced melanoma cell invasion. The latter effect could be rescued by the addition of recombinant WNT5A. Notably, immunoprecipitation analysis revealed that only the p38α-MAPK isoform was activated by IL-6, and subsequent siRNA silencing of p38α-MAPK abolished the IL-6-induced up-regulation of WNT5A. Taken together, we demonstrate a novel link between the two melanoma pro-metastatic agents IL-6 and WNT5A explaining how IL-6 can increase melanoma cell invasion and thus promote the metastatic process. This finding provides a basis for future therapeutic intervention of melanoma progression.
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| 43. |
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| 44. |
- Pousette, Jenny, et al.
(författare)
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Prognostic and Predictive Significance of Stromal Tumor-Infiltrating Lymphocytes (sTILs) in ER-Positive/HER2-Negative Postmenopausal Breast Cancer Patients
- 2022
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Ingår i: Cancers. - : MDPI. - 2072-6694. ; 14:19
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Tidskriftsartikel (refereegranskat)abstract
- The clinical impact of tumor-infiltrating lymphocytes (TILs) is less known for breast cancer patients with the estrogen receptor-positive (ER+)/human epidermal growth factor receptor-negative (HER−) subtype. Here, we explored the prognostic and predictive value of TILs regarding distant recurrence-free interval (DRFI) and breast cancer-specific survival (BCSS) in 763 postmenopausal patients randomized to receive tamoxifen vs. no systemic treatment. TILs were assessed in whole section tumor samples stained with H&E and divided into low (<10%), intermediate (10–39%), or high (≥40%). High TILs were associated with poor prognostic variables and good prognoses for all patients, but not within the ER+/HER2− group. Within the ER+/HER2− group, high gene expression of CD19 and PD-L1 and high IMMUNE1 score indicated good prognosis in multivariable analysis while high CD8 and CD19 gene expression and high IMMUNE1 score were associated with less tamoxifen benefit. These results indicate that within the ER+/HER2− subtype there could be subsets of patients where expression of specific TIL markers might be used to reveal candidates for immune therapy interventions upon failure of the endocrine therapy.
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| 45. |
- Rydhög, Björn, et al.
(författare)
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Assessing compliance with Paleolithic diet by calculating Paleolithic Diet Fraction as the fraction of intake from Paleolithic food groups
- 2019
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Ingår i: Clinical Nutrition Experimental. - : Elsevier BV. - 2352-9393. ; 25, s. 29-35
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dietary compliance assessments are absent in clinical studies on Paleolithic diet. We therefore developed a ‘Paleolithic Diet Fraction’ (PDF), calculated as the fraction of intake from Paleolithic food groups, to assess compliance with Paleolithic diet in a previously reported study. Methods: 29 male patients with ischemic heart disease, impaired glucose tolerance and waist circumference > 94 cm, were randomized to a Paleolithic or Mediterranean-like diet for 12 weeks. Mean daily PDFs were calculated for dietary energy and weight for all participants using four-day weighed food records, and linear regression analysis was performed between PDF and primary outcome measures plus leptin for both diet groups combined. Results: PDFs were just above 80% for the Paleolithic diet group and around 40% for the Mediterranean-like diet group. We found associations between PDF and outcome measures of similar strength as previously reported for group differences, and an association with weight, for which no group difference was previously found. Conclusions: Calculation of PDF demonstrated a mean compliance of just above 80% in the Paleolithic diet group and association studies indicated a clinical relevance for PDF. Trial registration: ClinicalTrials.gov NCT00419497 retrospectively registered.
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| 46. |
- Rydhög, Björn, et al.
(författare)
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Inverse association between Paleolithic Diet Fraction and mortality and incidence of cardiometabolic disease in the prospective Malmö Diet and Cancer Study
- 2024
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Ingår i: European Journal of Nutrition. - 1436-6207. ; 63:2, s. 501-512
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: Paleolithic Diet Fraction (PDF) estimates how large a portion of the absolute dietary intake stems from food groups included in the Paleolithic diet. In randomized controlled trials higher PDFs have been associated with healthier levels of cardiometabolic risk markers. Our aim was to build upon these findings by examining associations between PDF and mortality and incidence of cardiometabolic disease in the prospective Malmö Diet and Cancer Study. Methods: PDF was calculated from an interview-based, modified diet history method, and associations were estimated by using multivariable Cox proportional hazards regression. The examined cohort consisted of 24,104 individuals (44–74 years, 63% women) without previous coronary events, diabetes, or stroke at baseline (1992–1996). A total of 10,092 individuals died during a median follow-up of 18 years. Results: Median PDF was 40% (0–90%). The adjusted hazard ratios (HR) for PDF as a continuous variable (from 0 to 100%) were for risk of death from all causes 0.55 [95% CI 0.45, 0.66], tumor 0.68 [95% CI 0.49, 0.93], cardiovascular 0.55 [95% CI 0.39, 0.78], respiratory 0.44 [95% CI 0.21, 0.90], neurological 0.26 [95% CI 0.11, 0.60], digestive, 0.10 [95% CI 0.03, 0.30], and other diseases 0.64 [95% CI 0.41, 1.00]. The corresponding HR for risk of coronary event was 0.61 [95% 0.43, 0.86], for ischemic stroke it was 0.73 [95% 0.48, 1.09] and for type 2 diabetes it was 0.82 [95% 0.61, 1.10]. Conclusion: Observational data suggest an inverse association between PDF and all-cause as well as cause-specific mortality and incidence of cardiometabolic disease.
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| 47. |
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| 48. |
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| 49. |
- Simkó, Attila, et al.
(författare)
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Towards MR contrast independent synthetic CT generation
- 2024
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Ingår i: Zeitschrift für Medizinische Physik. - : Elsevier. - 0939-3889 .- 1876-4436. ; 34:2, s. 270-277
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Tidskriftsartikel (refereegranskat)abstract
- The use of synthetic CT (sCT) in the radiotherapy workflow would reduce costs and scan time while removing the uncertainties around working with both MR and CT modalities. The performance of deep learning (DL) solutions for sCT generation is steadily increasing, however most proposed methods were trained and validated on private datasets of a single contrast from a single scanner. Such solutions might not perform equally well on other datasets, limiting their general usability and therefore value. Additionally, functional evaluations of sCTs such as dosimetric comparisons with CT-based dose calculations better show the impact of the methods, but the evaluations are more labor intensive than pixel-wise metrics.To improve the generalization of an sCT model, we propose to incorporate a pre-trained DL model to pre-process the input MR images by generating artificial proton density, T1 and T2 maps (i.e. contrast-independent quantitative maps), which are then used for sCT generation. Using a dataset of only T2w MR images, the robustness towards input MR contrasts of this approach is compared to a model that was trained using the MR images directly. We evaluate the generated sCTs using pixel-wise metrics and calculating mean radiological depths, as an approximation of the mean delivered dose. On T2w images acquired with the same settings as the training dataset, there was no significant difference between the performance of the models. However, when evaluated on T1w images, and a wide range of other contrasts and scanners from both public and private datasets, our approach outperforms the baseline model. Using a dataset of T2w MR images, our proposed model implements synthetic quantitative maps to generate sCT images, improving the generalization towards other contrasts. Our code and trained models are publicly available.
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| 50. |
- Skau, Tommy, et al.
(författare)
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Prevalence of symptomatic leg ischaemia in a swedish community : an epidemiological study
- 1993
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Ingår i: European Journal of Vascular Surgery (United Kingdom). - 0950-821X. ; 7:4, s. 432-437
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Tidskriftsartikel (refereegranskat)abstract
- The prevalence of symptomatic leg ischaemia (SLI) was studied using a standardised postal questionnaire and by measuring ankle systolic blood pressure among those with leg pain. All individuals, aged 50–89 years, of both sexes (n = 2748) in a community of 7524 inhabitants were included. The overall questionnaire response rate was 92%, of whom 441 (17%) reported any form of leg pain. Ankle systolic blood pressure (ASBP) was measured in 353 (80%) of those. Ankle/brachial index (ABI) ⩽0.8 was chosen as the criterion for verified SLI. One hundred and seven (30%) had a verified SLI (ABI ⩽0.8).Hospital records could be reviewed in 83% of the non-responders, and revealed corresponding distributions of risk factors among the non-responders and the questionnaire-responders. Risk factor frequencies among ASBP-examined and not examined individuals were also comparable. The overall prevalence of SLI in the age 50–89 years was 4.1%, ranging from 1.5% in the age decade of 50–59 years, to maximum 7.1% in the decade 70–79 years. A slight but not significant male predominance was recorded, except for the age decade 70–79 years. The prevalence of SLI in the whole community population was approximately 2000/100 000 of which 5% were possible candidates for vascular intervention.
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